Further studies in developing means of delaying the onset of sugar cataracts have led to a new series of compounds known as flavonoids. These compounds, ubiquitously distributed in plants, were found to be effective inhibitors of lens aldose reductase, the enzyme which initiates the cataractous process in diabetes and galactosemia. The inhibitory activities of the flavonoids, quercetin, quercitrin and myricitrin, even surpassed those of AY-22,284 and TMG, the previously known inhibitors. The degree of inhibition was observed to differ with variation in the structure of the flavonoid moiety. Kinetic studies indicated that the inhibition of the enzyme by flavonoids is of the noncompetitive type. The flavonoids were also effective in blocking accumulation of polyol in rat lenses incubated in high sugar medium. At 10 to the minus 4th power M, the polyol accumulation was decreased by 80% with quercitrin and by 40% with AY-22,284 as compared to contralateral controls. At 10 to the minus 5th power and 10 to the minus 6th power M, quercitrin reduced the polyol synthesis by about 30% and 20% respectively, while AY-22,284 was ineffective at these concentrations. These results indicate that flavonoids are the most potent aldose reductase inhibitors available so far. Since there are so many possible forms of flavonoids, further studies of these compounds may reveal a potentially useful agent for delaying or preventing the onset of sugar cataracts.